The Chicago Multicenter AIDS Cohort Study (MACS) has made important contributions to the understanding of the natural history of treated and untreated HIV-1 infection. Continuation of the study into the era of widespread use of highly active antiretroviral therapy (HAART) allowed for the evaluation of the benefits of potent therapy, however, prolonged HIV-1 infection and/or the adverse effects of treatment could impact these benefits. The expanded cohort including 275 younger, predominantly African-American and Hispanic men, more accurately reflects the demographics of the epidemic in 2003 and allows for comparisons across racial, ethnic and age groups. The specific aims of the MACS for the next 5 years are to: i) assess the population effectiveness of long term HAART use and whether it is influenced by race/ethnicity; ii) delineate the heterogeneity and determinants of individual responses to HAART, with particular emphasis on the durability of the response in differing racial/ethnic and age groups; iii) determine the frequency of metabolic and cardiovascular adverse effects of HIV-1 and HAART; iv) characterize host genetic factors that distinguish long term non- and slow progressors from more rapid progressors prior to the use of HAART; v) further characterize the nature of resistance to infection in uninfected, highly exposed participants; vi) evaluate the impact of HAART, adherence, socioeconomic status, race/ethnicity and duration of HIV-infection on neurological outcomes and neuropsychological functioning; vii) examine the effect of co-infections, hepatitis B and C, and GB virus type C on the progression of HIV-1 infection and the response to HAART; viii) elucidate the pidemiology and pathogenesis of HIV-1 related malignant disease and the role of viral co-infections such as human herpesvirus type 8 and Epstein Barr virus; ix) continue to develop and implement innovative methods for the design and analysis of cohort studies of HIV/AIDS; x) continue to provide a platform for pathogenesis and other collaborative research. The Chicago investigators will contribute to each of these specific aims through maintenance of the cohort, core laboratories, capacity for data management and analysis, and active participation in the Executive Committee and Working Groups which develop the scientific agenda of the overall study,